From:  Therapeutic role of probiotics in motor and non-motor symptoms of Parkinson’s disease

 Mechanistic pathways and therapeutic effects of microbiome-targeted interventions in PD.

Microbiota-targeted strategyMechanistic pathwaysExamplesReferences
Dietary interventions
  • ↑ SCFAs improve blood-brain and intestinal barrier integrity.

  • ↓ Intestinal dysbiosis and ↑ butyrate-producing bacteria, reducing neuroinflammation.

  • Induce immune modulation and ↓ oxidative stress.

High-fiber diet and Mediterranean diet.[27, 42, 63, 64]
Prebiotics
  • Stimulate growth of Bifidobacterium and Lactobacillus, ↑ butyrate, supporting dopaminergic neuron survival.

  • ↓ Intestinal permeability and endotoxin translocation, reducing microglial activation.

  • ↓ Neuroinflammation through inhibition of the TLR4/NF-κB pathway, improving motor and non-motor symptoms.

Resistant fermentable fiber blend (starch and inulin).[6467]
Fecal microbiota transplantation (FMT)
  • Restores microbial diversity and gut barrier integrity via gut-brain axis modulation.

  • ↑ SCFAs and ↓ α-syn aggregates, protecting dopaminergic neurons.

Randomized placebo-controlled trial of FMT improves autonomic symptoms in PD.[68, 69]
Specific microbial therapies
  • Activate neurotrophic pathways (BDNF, PI3K) and inhibit pro-inflammatory cascades.

  • Promote dopaminergic neuron survival and neuroprotection.

Targeted or engineered strains (e.g., next-generation probiotics, bacteriophages, SCFA-producing bacteria).[64, 70, 71]
Probiotics
  • Live microorganisms that rebalance gut microbiota and enhance intestinal barrier integrity.

  • ↑ SCFAs modulate microglial activity, ↓ oxidative stress, and support dopaminergic neuron survival.

  • Indirectly act on the gut-brain axis by producing neuroactive metabolites and ↓ pro-inflammatory cytokines.

Lactobacillus + Bifidobacterium regimens.[27, 72]

α-syn: alpha-synuclein; SCFAs: short-chain fatty acids; PD: Parkinson’s disease.